Hydrochloric Acid → HCID 86724279, compound

HRID 873733Notes

Reaction equation

HRID 873733 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[O:30][C:29]([CH3:35])([CH3:34])[C:25]1([CH2:28][O:27][CH2:26]1)[C@@:5]12[CH2:9][O:8][C:7]([N:10]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])C(OC(C)(C)C)=O)=[N:6]1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:58][Si](C)(C)C)(C)C.[Li+].Cl>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C(Cl)(Cl)Cl>[NH2:58][C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[O:30][C:29]([CH3:34])([CH3:35])[C:25]1([CH2:28][O:27][CH2:26]1)[C@@:5]12[CH2:9][O:8][C:7]([NH:10][C:18](=[O:19])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:6]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86724273HCID 86724273, compound

Product 1

HCID 86724279HCID 86724279, compoundYield 99.5%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 6212ChloroformSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of di-tert-butyl [(4S)-6′-bromo-2′,2′-dimethyldispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl]imidodicarbonate (3.40 g, 6.14 mmol), bis(dibenzylideneacetone)palladium(0) (353 mg, 0.614 mmol), and tri-tert-butylphosphonium tetrafluoroborate (179 mg, 0.617 mmol) was added lithium bis(trimethylsilyl)amide (1M solution in toluene, 31 mL, 31 mmol) at ambient temperature under argon atmosphere. After stirring for 1.5 hours at 60° C., the mixture was cooled in an ice-water bath and 1M aqueous HCl (31 mL) was added. After stirring for 10 minutes at ambient temperature, to the mixture was added CHCl3, and the mixture was filtered through a pad of celite. The filtrate was separated and the aqueous layer was extracted with CHCl3. The combined organic layer was dried over Na2SO4 and filtered. The filtrate was concentrated at reduced pressure. To the residue were added MeOH (34 mL) and silica gel (neutral; 17 g) at ambient temperature. After stirring for 1 hour at 40° C., the mixture was concentrated at reduced pressure. The residue was purified with column chromatography on silica gel (hexane-EtOAc, a linear gradient of EtOAc from 10 to 100%) to afford tert-butyl [(4S)-6′-amino-2′,2′-dimethyldispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl]carbamate (2.38 g).

Workup

  1. temperaturethe mixture was cooled in an ice-water bath
  2. stirringAfter stirring for 10 minutes at ambient temperature, to the mixture
  3. filtrationthe mixture was filtered through a pad of celite
  4. customThe filtrate was separated
  5. extractionthe aqueous layer was extracted with CHCl3
  6. dry with materialThe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated at reduced pressure
  9. additionTo the residue were added MeOH (34 mL) and silica gel (neutral; 17 g) at ambient temperature
  10. stirringAfter stirring for 1 hour at 40° C.
  11. concentrationthe mixture was concentrated at reduced pressure
  12. customThe residue was purified with column chromatography on silica gel (hexane-EtOAc

Sources & evidence

ORD record
ord-7dc90d0fdd994ef3abb4b855803cf42f
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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